ETIDIOH - NEW

  Abstract Background :  Avian influenza of the H5N1 subtype shares substantial relatedness in its neuraminidase (NA) surface protein with human influenza A H1N1 viruses of the past century. Understanding variation in pre-existing anti-N1 antibodies against H5N1 is critical to pandemic risk assessment and preparedness.  Methods :  We used anonymized, residual sera collected equally from ten age groups spanning one to >80 years during an August 2024 cross-sectional serosurvey in British Columbia, Canada . We assessed NA inhibition antibody titres by enzyme-linked lectin assay against H5N1 (N=575), H1N1pdm09 (N=250) and H3N2 (N=205). We compared anti-NA titres by birth (imprinting) cohorts defined in relation to historic N1 and/or N2 exposure opportunities.  Results :  Among participants with median age 32 (IQR: 15-62) years, 404 ( 70%) had cross-reactive anti-N1 titre ≥10 against H5N1 , with 260 (45%), 182 (32%) and 98 (17%), having titres ≥40, ≥80 and ≥...

  Abstract Since winter 2022/23, high pathogenicity avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b, genotype euBB, has caused extensive mortality among wild birds . This genotype emerged in France in spring 2022 through reassortment between a gull-adapted low-pathogenicity virus and HPAIV H5N1. Phylogeographic and spatiotemporal analyses show that transmission into German breeding colonies of black-headed gulls (Chroicocephalus ridibundus) and common terns (Sterna hirundo) involved multiple independent incursions, likely via black-headed gulls returning from wintering grounds in the Netherlands, Belgium, and France . It spilled over into common terns, which breed in shared colonies with black-headed gulls, and led to high adult mortality in both species in 2023 (at least 8,137 black-headed gulls and 614 common terns; >3% of the breeding population), followed by significant breeding pair declines in 2024 (-15.9% in black-headed gulls, -5.8% in common terns). Increased immunity...

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  Abstract Influenza A viruses (IAV) remain a persistent One Health threat, and whole-genome sequencing from wastewater offers a promising surveillance tool . However, IAV is at low abundance in wastewater , making it difficult to sequence. We benchmarked four targeted enrichment methods suited for whole-genome sequencing including custom and off-the-shelf amplicon and probe-based methods. Our custom HA tiled-amplicon panel was sensitive, fast, and cost-effective, making it suitable for monitoring low-abundance seasonal variants of known subtypes . However, its reliance on conserved and intact primer-binding sites limited primer design to fewer subtypes. A previously published universal amplicon method targeted all IAV subtypes , but it performed poorly in wastewater due to its reliance on intact genome segments. Probe-capture methods were resilient to RNA degradation and mismatches , potentially enabling broader surveillance and detection of emerging strains. However, probes were ...

  Abstract Influenza A viruses remain a global health threat, yet no universal antibody therapy exists . Clinical programs have centered on neutralizing mAbs , only to be thwarted by strain specificity and rapid viral escape . We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e). Combined at low dose, this “triple M2e-mAb” confers robust prophylactic and therapeutic protection in mice challenged with diverse human and zoonotic IAV strains, including highly pathogenic variants. Therapeutic efficacy depends on Fc-mediated effector activity via FcγRI, FcγRIII, and FcγRIV, rather than in vitro neutralization. Serial passaging in triple M2e-mAb–treated immunocompetent and immunodeficient hosts failed to generate viral escape mutants. Our findings redefine the influenza-specific antibody therapeutic design and support Fc-optimized, non-neutralizing M2e-mAbs as a broadly effective, mut...